Acta Pharmacologica Sinica 2008 May; 29 (5): 634-640; doi: 10.1111/j.1745-7254.2008.00755.x

Aim: To screen for interferon (IFN) α-2b mimetic peptides with antiviral activity.

Methods: Selecting IFN receptor-binding peptides from a phage-display heptapeptide library using a novel functional biopanning method. This method was developed to identify peptides with activity against vesicular stomatitis virus (VSV) inducing cytopathic effects on WISH cells.

Results: Sixteen positive clones were obtained after 3 rounds of functional selection. Ten clones were picked from these positive clones according to the results of phage ELISA and were sequenced. The amino acid sequences homologous to IFNα-2b were defined by residues AB loop 31-37, BC loop 68-74, C helix 93-99, CD loop 106-112, D helix 115-121, DE loop 132-138, and E helix 143-161. Two of the peptides, designated clones T3 and T9, aligned with the IFNAR2-binding domains (AB loop and E helix), were synthesized and designated as IR-7 and KP-7, respectively. Both KP-7 and IR-7 were found to compete with GFP/IFNα-2b for receptor binding and mimicked the antiviral activity of IFNα-2b cooperatively.

Conclusion: Two IFNα-2b mimetic peptides with antiviral activity were derived from a phage-display heptapeptide library using a novel functional selection method.

Keywords: interferon α-2b; mimetic peptide; random peptide library; type I interferon receptor; functional selection